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Open Access Macedonian Journal of Medical Sciences. 2019 Apr 15; 7(7):1053-1058.
https://doi.org/10.3889/oamjms.2019.242
eISSN: 1857-9655
Basic Science
*
Oleksandr Litus, Nadiya Derkach, Viktor Litus, Yuriy Bisyuk, Bohdan Lytvynenko
Abstract
Citation: Litus O, Derkach N, Litus V, Bisyuk Y, BACKGROUND: The C-159T polymorphism of the CD14 receptor gene can be associated with the development
Lytvynenko B. Efficacy of Probiotic Therapy on Atopic
Dermatitis in Adults Depends on the C-159T
of atopic dermatitis. Probiotics can modulate chronic inflammation through activation of the CD14 receptor. So,
Polymorphism of the CD14 Receptor Gene - A Pilot the efficacy of probiotic therapy can be dependent on this genetic polymorphism.
Study. Open Access Maced J Med Sci. 2019 Apr 15;
7(7):1053-1058. https://doi.org/10.3889/oamjms.2019.242 AIM: The purpose of the study was to investigate the efficacy of adding probiotic (Lactobacillus acidophilus, LA-5
Keywords: Atopic dermatitis; Probiotics; C-159T and Bifidobacterium animalis subsp. lactis, ВВ-12) to standard treatment (ointment of fluticasone propionate
polymorphism; Cytokines
0.005% and emollient) of atopic dermatitis in adults during 28 days, depending on the stratification of patients on
*Correspondence: Bohdan Lytvynenko. Shupyk National
Medical Academy of Postgraduate Education, Kiev,
CC or TT genotypes of the CD14 receptor gene.
Ukraine. E-mail: libovi@gmail.com
MATERIAL AND METHODS: The study included 37 adult patients with AD. There were identified 19 patients with
Received: 14-Feb-2019; Revised: 22-Mar-2019;
Accepted: 23-Mar-2019; Online first: 10-Apr-2019 exogenous (IgE-dependent) and 18 with endogenous (IgE-dependent) AD. To evaluate the efficacy of the
Copyright: © 2019 Oleksandr Litus, Nadiya Derkach, probiotics all patients were divided into three groups for both exogenous and endogenous AD. The first group was
Viktor Litus, Yuriy Bisyuk, Bohdan Lytvynenko. This is an selected from patients with CC genotype (C-159T) who received standard therapy (ointment of fluticasone
open-access article distributed under the terms of the
Creative Commons Attribution-NonCommercial 4.0
propionate 0.005% – 2 times a day, emollients – 2 times a day) and probiotic (Lactobacillus acidophilus, LA-5 and
International License (CC BY-NC 4.0). Bifidobacterium animalis subsp. lactis, ВВ-12 - 1 capsule 2 times per day) The second group included patients
Funding: This research did not receive any financial with CC genotype, who received only standard therapy. The third group was presented by patients with TT
support genotype (C-159T) who received standard therapy and probiotic. The SCORAD and DLQI parameters were
Competing Interests: The authors have declared that no evaluated on Day 0, 14 and 28. The level of IL-4, IL-5, IL-10, TGF-β cytokines was determined on Day 0 and Day
competing interests exist 28.
RESULTS: The results of our study found that the addition of probiotics (Lactobacillus acidophilus, LA-5 and
Bifidobacterium animalis subsp. lactis, ВВ-12) to standard treatment (ointment of fluticasone propionate 0.005%,
emollient) significantly increased the effectiveness of treatment of atopic dermatitis in adults with exogenous form
and CC genotype (C-159T), confirmed by clinical (a significant decrease of SCORAD and DLQI indices) and
immunological criteria (a significant decrease of IL-4 and an increase of TGF-β).
CONCLUSION: Simultaneous determination of the exogenous or endogenous form, identification of the C-159T
genotypes, evaluation of the serum level of IL-4 and TGF-β can serve as an algorithm for the personalised
treatment of patients with atopic dermatitis.
Open Access Maced J Med Sci. 2019 Apr 15; 7(7):1053-1058. 1053
Basic Science
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nucleotides [3]. In the same locus, there are genes Material and Methods
responsible for the synthesis of IgE. There are many
studies of the C-159T polymorphism (rs2569190) of
the CD14 receptor gene in atopic patients [4]. For this The study included 37 adult patients with AD.
polymorphism, cytosine (C) is replaced by thymine (T) For the diagnosis of atopic dermatitis, we used the
at position 159 of the promoter region, resulting in the recommendations provided by the European
population presence of homozygotes of cytosine and Academy of Dermatology and Venereology [15].
thymine (CC, TT) and heterozygotes cytosine-thymine
(CT) [3] All patients with atopic dermatitis, depending
on the level of total IgE and at least one allergen's
This polymorphism can affect the positivity by skin prick tests, were divided into two
development of various diseases in different ways. main groups: exogenous or IgE-dependent AD (total
The risk of nasal allergies and atopy was the most IgE level greater than 100 IU/ml) and endogenous
reduced in the subjects who combined both an early- IgE-independent AD (total IgE level less than 100
life exposure to a farming environment and the - IU/ml). The level of total IgE was determined by
159TT genotype [5]. Although сhildren with C/C ELISA method.
variant of CD14 C-159T had a significantly lower
prevalence of croup [6]. There were identified 19 patients with
exogenous (IgE-dependent) and 18 with endogenous
It has been shown that the number of positive (IgE-dependent) AD.
skin tests was significantly higher in patients with CC
genotype compared with TT [3]. In the Netherlands, it Allele-specific PCR with electrophoretic
was found that in patients with positive skin tests, the detection was used to access gene polymorphisms of
level of total IgE was significantly (p < 0.05) higher in the CD14 receptor (C-159T, rs2569190). Allele-
CC compared to TT genotype [7]. In Australia, it was specific PCR was performed using kit: "Mutation of
found that the risk of atopy in children is significantly monocyte differentiation antigen (CD14) C-159T"
higher in CC genotype (OR = 2.0, P = 0.04) [8]. In (Lytech, Russia) according to the manufacturer's
China, one study has shown that atopic subjects with instructions.
CC genotype had the highest serum total IgE levels The level of IL-4, IL-5, IL-10, TGF-β in serum
compared with CT and TT genotypes [9]. Another was determined by ELISA method.
research has shown that TT homozygotes are more
common in adult patients with allergic rhinitis among Determination of the severity of the disease
the Chinese population and the C-159T polymorphism was carried out using SCORAD (SCORing Atopic
was not associated with serum IgE levels [10]. Other Dermatitis) index [16]. The quality of life of the
studies indicate that C-159T gene polymorphism can patients was assessed using the DLQI questionnaire
be associated with elevated levels of soluble CD14 (Dermatitis Quality of Life Index) [17].
[11], [12]. The clinical trial was conducted as open,
In turn, probiotics have antagonistic properties controlled, randomised, in 6 parallel groups during 28
regarding activation mechanisms of inflammation, days at the departments of dermatology and clinical,
including endotoxin-dependent ones. So, probiotics laboratory immunology and Allergology of the Shupyk
stimulate regulatory T-lymphocytes, increase the National Medical Academy of Postgraduate
synthesis of IF-β and TGF-β, inhibit the function of T- Education.
helper type 2, reduce the secretion of TNF-α and To study the efficacy of the probiotics
eosinophilic cationic protein, reduce the concentration (Lactobacillus acidophilus, LA-5 and Bifidobacterium
of total and specific IgE, reduce colonisation of the animalis subsp. lactis, ВВ-12) on the severity of the
skin by Staphylococcus aureus and restore its barrier disease, quality of life and immune parameters,
function [13]. genotypes of CC and TT, all patients were divided into
Identifying phenotypes and genotypes, on the three groups for both exogenous and endogenous
one hand, and potential biomarkers on the other, are AD. The first groups were selected from patients with
vital elements for the successful development of new CC genotype (C-159T) who received standard therapy
and personalised therapeutic approaches in patients (ointment of fluticasone propionate 0.005% – 2 times
with AD [14]. a day, emollients – 2 times a day) and probiotic
(Lactobacillus acidophilus, LA-5 and Bifidobacterium
The purpose of the study was to investigate animalis subsp. lactis, ВВ-12 - 1 capsule 2 times per
the efficacy of adding probiotic (Lactobacillus day) The second group included patients with CC
acidophilus, LA-5 and Bifidobacterium animalis subsp. genotype, who received only standard therapy. The
lactis, ВВ-12) to standard treatment (ointment of third group was presented by patients with TT
fluticasone propionate 0.005% and emollient) of atopic genotype (C-159T) who received standard therapy
dermatitis in adults during 28 days, depending on the and probiotic. The SCORAD and DLQI parameters
stratification of patients on CC or TT genotypes of the were evaluated on Day 0, 14 and Day 28. The level of
CD14 receptor gene. IL-4, IL-5, IL-10, TGF-β cytokines was determined on
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1054 https://www.id-press.eu/mjms/index
Litus et al. Efficacy of Probiotic Therapy on Atopic Dermatitis in Adults Depends on the C-159T Polymorphism of the CD14 Receptor Gene
_______________________________________________________________________________________________________________________________
Day 0 and Day 28. with probiotics during 28 days significantly reduced
the SCORAD index in exogenous AD patients with CC
All results were analysed using "Minitab 16"
and TT genotypes (Table 1). Patients with CC
statistical software. In the analyses, the normality test
genotype who received standard therapy with
was done using the Kolmogorov-Smirnov test. The
probiotics had the most significant reduction of
comparison of central tendencies of two independent
SCORAD index on Day 28.
samples was performed using the U-Mann-Whitney
test. Comparison of the average of two independent Table 2: The dynamics of DLQI scores in patients that
samples used Student's criterion for non-normally and underwent the different treatments
normally distributed samples, respectively. Groups Day 0 Day 14 Day 28 P1
Quantitative variables are presented as mean values Exogenous СС genotype, 10.00 (7.50- 7.00 (4.50- 3.00 (2.00- 0.001
AD standard therapy + 15.53) 10.01)# 3.50)#
and standard deviation (SD) or 95% confidence probiotics, n = 7
intervals for normally distributed data, and the median СС genotype, 9.50 (7.19- 6.50 (5.19- 4.50 (3.19- 0.037
standard therapy, n = 19.06) 15.25) 12.45)*#
with first (Q1) and third (Q3) quartile or 95% 6
TT genotype, 12.50 (6.19- 9.50 (4.19- 6,00 (3.19- 0.150
confidence intervals for non-normally distributed data. standard therapy + 21.42) 14.81) 11.61)*
For multiple comparisons, the Kruskal-Wallis test and probiotics, n = 6
P2 0.841 0.715 0.012
ANOVA (Bonferroni and Sheffe correction) were used. Endogenous СС genotype, 12.50 (6.39- 8,50 (5.00- 5,50 (3.19- 0.034
AD standard therapy + 19.42) 13.42) 8.42)#
All study subjects provided written informed probiotics, n = 6
СС genotype, 11.00 (7.39- 7.00 (4.19- 4.50 (3.19- 0.027
consent to participate in this research. Ethics approval standard therapy, n = 17.42) 11.81) 8.81)#
6
was received from the Bioethics Committee of the TT genotype, 13.50 (8.19- 10.00 (6.19- 6.00 (4.19- 0.031
Shupyk National Medical Academy of Postgraduate standard therapy + 19.42) 13.81 9.81)#
probiotics, n = 6
Education, Kyiv, Ukraine. P2 0.816 0.442 0.544
Note: same as in Table 1.
Open Access Maced J Med Sci. 2019 Apr 15; 7(7):1053-1058. 1055
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The lowest score was observed in patients with CC Table 6: The serum level of TGF-β (pg/ml) in patients that
underwent different treatments
genotype (standard treatment + probiotics), which
significantly differed (p = 0.012) from other groups in Groups Day 0 Day 28 P1
Exogenous AD СС genotype, 16.10 35.90 0.001
the exogenous form of AD. standard therapy + (13.69-21.61)* (28.64-47.48)#
probiotics, n = 7
Dynamics of the concentration of IL-4 is СС genotype, 17.40 18.30 0.998
standard therapy, n = 6 (12.91-25.43)* (13.84-20.10)*#
provided in Table 3. TT genotype, 41.90 39.85 0.998
standard therapy + (31.81-50.34) (32.66-52.83)
probiotics, n = 6
On Day 0, the serum level of IL-4 (Table 3) in P2 0.003 0.002
patients with TT genotype was significantly lower Endogenous AD СС genotype, 16.70 18.20 0.818
standard therapy + (11.12-32.59)* (12.84-29.77)*
compared to CC genotype in both groups for probiotics, n = 6
exogenous and endogenous AD. On Day 28 (Table СС genotype, 17.75 17.95 0.810
standard therapy, n = 6 (13.17-26.64)* (12.12-29.88)*
3), there was a significant decreased (p = 0.004) of TT genotype, 46.90 46.85 0.631
standard therapy + (34.86-50.23) (37.12-53.04)
this cytokine only in patients with CC genotype and probiotic, n = 6
exogenous form of AD who received standard therapy P2 0.003 0.003
Note: same as in Table 3.
with probiotics. For endogenous AD, no such
significant changes have been observed.
The dynamics of TGF-β in contrast to IL-10
Table 4: The serum level of IL-5 (pg/ml) in patients that was different. Thus, in patients with CC genotype and
underwent different treatments
exogenous form of AD (Table 6) who received
Groups Day 0 Day 28 P1 standard treatment and probiotics, the level of TGF-β
Exogenous AD СС genotype, 30.70 23.10 0.074
standard therapy + (23.18-43.16)* (16.74-35.14)* (p = 0.001) was significantly increased by Day 28
probiotics, n = 7
СС genotype, 28.80 24.50 0.132
compared to Day 0. Also, the level of TGF-β in this
standard therapy, n = 6 (20.68-44.06)* (15.72-34.93)* group on Day 28 did not significantly differ from the
TT genotype, 20.50 13.85 0.240
standard therapy + (10.64-25.46) (9.62-21.56) group with TT genotype. In all other cases, the
probiotics, n = 6
P2 0.023 0.048
concentration of this cytokine in TT genotype (Table
Endogenous AD СС genotype, 28.10 24.65 0.394 6) was significantly higher compared to CC genotype.
standard therapy + (20.59-45.97)* (15.64-37.95)*
probiotics, n = 6
СС genotype, 35.40 29.85 0.240
standard therapy, n = 6 (29.87-48.62)* (24.59-39.20)*
TT genotype, 15.80 12.40 0.379
standard therapy + (9.77-23.45) (8.86-18.91)
probiotics, n = 6
P2 0.003 0.004
Note: same as in Table 3.
Discussion
1056 https://www.id-press.eu/mjms/index
Litus et al. Efficacy of Probiotic Therapy on Atopic Dermatitis in Adults Depends on the C-159T Polymorphism of the CD14 Receptor Gene
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Open Access Maced J Med Sci. 2019 Apr 15; 7(7):1053-1058. 1057
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